The eccentric cleavage product of β-carotene, β-apo-13-carotenone, functions as an antagonist of RXRα

In this study, we investigated the effects of eccentric cleavage products of beta-carotene, i.e. beta-apocarotenoids (BACs), on retinoid X receptor alpha (RXR alpha) signaling. Transactivation assays were performed to test whether BACs activate or antagonize RXR alpha. Reporter gene constructs (RXRE-Luc, pRL-tk) and RXR alpha were transfected into Cos-1 cells and used to perform these assays. None of the BACs tested activated RXR alpha. Among the compounds tested, beta-apo-13-carotenone was found to antagonize the activation of RXR alpha by 9-cis-retinoic acid and was effective at concentrations as low as 1 nM. Molecular modeling studies revealed that beta-apo-13-carotenone makes molecular interactions like an antagonist of RXR alpha. The results suggest a possible function of BACs on RXR alpha signaling. (C) 2010 Elsevier Inc. All rights reserved.